Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The Genius of a Disorderly Enzyme

28.06.2011
USC Dornsife researchers uncover how the inefficiency of activation-induced deoxycytidine deaminase is good for your immune system.

Why is antibody diversity important? Think about it like this, said Myron Goodman: “Why don’t you die when I sneeze? It’s because you have a powerful immune system. And the way to get a decent immune system is for your body to have a way to respond to insults it has never seen before.”

Random patterns of deamination by the enzyme activation-induced deoxycytidine deaminase (AID) are the key to generating antibody diversity, a crucial component to a healthy immune system, according to a new study by USC Dornsife researchers published in The Journal of Biological Chemistry.

Having variation in the types of antibodies produced by your body gives it a fighting chance to respond to those “insults.” Antibodies protect against invasion by antigens such as bacteria or viruses by locating them in the body and neutralizing them. To do that, antibodies must bind to antigens. The more variation in the types of antibodies produced by the body, the more likely they will be able to bind to and fight off antigens, which come in many forms.

To create antibody diversity, mutations must occur in the variable region of immunoglobulin genes, the region where antibodies bind to invaders. Generating those mutations has to be a really random process according to Goodman, professor of biological sciences and chemistry in USC Dornsife. This is where AID steps in.

Goodman and his colleagues monitored the actions of AID as it scanned single-stranded DNA or transcribed double-stranded DNA. The enzyme essentially moves back and forth along the DNA strand and sporadically deaminates, or converts, cytosine to uracil triggering a mutation in tri-nucleotide motifs – sequences comprising three bases – found along the DNA.

Unlike most enzymes that are exquisitely efficient in targeting favored motifs, they found that AID was extremely inefficient. AID initiated chemical reactions in favored motifs only about 3 percent of the time. By mutating the motifs so haphazardly, the researchers suggest that AID produces antibody diversity.

The study also sheds light on a little-studied group of enzymes. Enzymes like AID that scan single-stranded DNA have been studied far less extensively than enzymes that scan double-stranded DNA.

“This is the first really clear picture of what AID is doing during the scanning process,” Goodman said.

To identify and describe AID’s complex process during scanning, the team used a genetic assay to measure the distribution of AID-induced mutations on individual DNA molecules and then analyzed the mutational data computationally using a random walk model, developed for the study by USC Dornsife researcher Peter Calabrese. By combining the genetic and computational analyses, they were able to calculate the distribution of mutations that occurred with a remarkable fit to their experimental data. The fit entailed matching theory to experiment for the patterns of closely spaced mutations and separately for the distances between mutated and non-mutated target motifs.

Their paper, “An Analysis of a Single-stranded DNA Scanning Process in which AID Deaminates C to U Haphazardly and Inefficiently to Ensure Mutational Diversity” published online May 12, was selected by The Journal of Biological Chemistry as a “Paper of the Week” to appear in the July 15 print issue. The distinction is bestowed by the publication’s editorial board members and associate editors to papers that represent the top 1 percent of papers reviewed in terms of significance and overall importance.

Authors on the paper are from USC Dornsife and include Phuong Pham, assistant professor (research) of biological sciences; Calabrese, assistant professor (research) of biological sciences; Goodman, professor of biological sciences and chemistry; and Soo Jung Park, research assistant. The National Institutes of Health funded the study.

Michelle Salzman | EurekAlert!
Further information:
http://www.usc.edu
http://dornsife.usc.edu/news/stories/972/the-genius-of-a-disorderly-enzyme

More articles from Life Sciences:

nachricht Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Bare bones: Making bones transparent

27.04.2017 | Life Sciences

Study offers new theoretical approach to describing non-equilibrium phase transitions

27.04.2017 | Physics and Astronomy

From volcano's slope, NASA instrument looks sky high and to the future

27.04.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>